The goal of this project is to delineate the mechanisms of host resistance to viral diseases. The principal model for these studies involves investigating the pathogenesis and neuroimmunology of rabies virus-infected mice, and ascertaining the mechanism(s) by which paralyzed mice abort their central nervous system infections and recover from disease. A sensitive and specific assay has been developed for determining the importance of cytolytic antibody in recovery from infection. It was found that mice which recovered from disease had high cytolytic antibody titers in brain, serum and cerebrospinal fluid. Genetic studies with inbred strains of mice have shown that A/WySn and A.SW/Sn mice were 100% susceptible to intraperitoneally injected rabies street virus, whereas SJL/J and CBA/J mice were 100% resistant. There was no evidence that resistance was H-2 linked or that sex-linked factor was of importance. Resistance was not manifested until mice were at least four weeks old. Studies with hybrid F1 generations indicated that resistance was dominant.